For Patients and Caregivers

POLARIX Trial Results: Additional Data

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POLARIX Primary Analysis
EFS & CR Select Secondary Endpoints
Exploratory 5-Year Subsequent Lymphoma Therapy Data

POLARIX primary analysis summary

The primary endpoint in the POLARIX clinical trial was investigator-assessed PFS (HR=0.73. 95% CI: 0.57, 0.95. p=0.0177). Additional efficacy endpoints were investigator-assessed EFS, objective response at end of treatment, and overall survival.1,15

EFS & CR: Select secondary endpoints

Primary analysis (ITT population): Superior EFS vs R-CHOP1,15,*
Patients with event, n (%)
POLIVY® + R-CHP (n=440) R-CHOP (n=439)
112 (26) 138 (31)
HR (95% CI)
POLIVY + R-CHP (n=440) R-CHOP (n=439)
0.75 (0.58, 0.96)
p-value†
POLIVY + R-CHP (n=440) R-CHOP (n=439)
0.0244
Primary analysis (ITT population): Superior EFS vs R-CHOP1,15,*
  POLIVY® + R-CHP (n=440) R-CHOP (n=439)
Patients with
event, n (%)		 112 (26) 138 (31)
HR (95% CI) 0.75 (0.58, 0.96)
p-value† 0.0244

*Modified EFS is defined as time from randomization to the earliest occurrence of disease progression, disease relapse, or death, an efficacy finding that led to non-protocol specified lymphoma treatment, or biopsy positive for residual disease.

†Stratified log-rank test, with a two-sided significance boundary of 0.05. The hierarchical testing order was PFS and modified EFS, then CR rate and OS.

Exploratory 5-year analysis data: EFS (ITT population)19,‡
Patients with event, n (%)
POLIVY + R-CHP (n=440) R-CHOP (n=439)
146 (33) 172 (39)
HR (95% CI)
POLIVY + R-CHP (n=440) R-CHOP (n=439)
0.78 (0.62, 0.97)
Exploratory 5-year analysis data: EFS (ITT population)19,‡
  POLIVY + R-CHP (n=440) R-CHOP (n=439)
Patients with
event, n (%)		 146 (33) 172 (39)
HR (95% CI) 0.78 (0.62, 0.97)

Limitations: No formal inferences may be drawn from these exploratory analyses. No statistical hypothesis testing was performed for the long-term follow-up data.

‡Data cutoff was July 5, 2024.

Primary analysis (ITT population): Objective response at EOT in patients receiving POLIVY + R-CHP vs R-CHOP1,§
Objective response rate, % (95% CI)
POLIVY + R-CHP (n=440) R-CHOP (n=439)
86 (82, 89) 84 (80, 87)
CR rate, %
POLIVY + R-CHP (n=440) R-CHOP (n=439)
78 (74, 82) 74 (70, 78)
Difference in CR rate, % (95% CI)
POLIVY + R-CHP (n=440) R-CHOP (n=439)
3.9 (-1.9, 9.7)
p-value†
POLIVY + R-CHP (n=440) R-CHOP (n=439)
0.1557
Primary analysis (ITT population): Objective response at EOT in patients receiving POLIVY + R-CHP vs R-CHOP1,§
  POLIVY + R-CHP (n=440) R-CHOP (n=439)
Objective response rate, % (95% CI) 86 (82, 89) 84 (80, 87)
CR rate, % 78 (74, 82) 74 (70, 78)
Difference in CR rate, % (95% CI) 3.9 (-1.9, 9.7)
p-valueII 0.1557

§By BICR, per 2014 Lugano response criteria.

||Cochran-Mantel-Haenszel chi-squared test, with a two-sided significance boundary of 0.01.

Subsequent lymphoma therapy: Exploratory 5-year analysis data

Patients receiving subsequent lymphoma therapy (ITT population)15,24,¶

Limitations: No formal inferences may be drawn from these 5-year observational data. These data on subsequent treatment were collected per protocol, but no formal analyses were conducted. POLARIX was a global trial: availability of subsequent therapy options and local practice patterns varied. NALT is dependent on the preferences of the prescribers and patients.

Data cutoff was July 5, 2024.
#Subsequent lymphoma treatment was defined as NALT and does not include R-CHOP or POLIVY + R-CHP.
**Including preplanned and unplanned.
††Includes any monotherapy, multidrug, or cell-based.

BICR = blinded independent central review; CAR-T = chimeric antigen receptor T-cell therapy; CI = confidence interval; CR = complete response; EFS = event-free survival; EOT = end of treatment; HR = hazard ratio; ITT = intention-to-treat; NALT = new anti-lymphoma therapy; OS = overall survival; PFS = progression-free survival; R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHP = rituximab, cyclophosphamide, doxorubicin, and prednisone.

NEXT: OS Results
Important Safety Information and Indication

Indication

POLIVY in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) is indicated for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater.

POLIVY in combination with bendamustine and a rituximab product (BR) is indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies.

Important Safety Information

Peripheral Neuropathy

POLIVY can cause severe peripheral neuropathy. Peripheral neuropathy occurs as early as the first cycle of treatment and is cumulative. POLIVY may exacerbate preexisting peripheral neuropathy.

In POLARIX, of 435 patients treated with POLIVY plus R-CHP, 53% reported new or worsening peripheral neuropathy, with a median time to onset of 2.3 months. Peripheral neuropathy was Grade 1 in 39% of patients, Grade 2 in 12%, and Grade 3 in 1.6%. Peripheral neuropathy resulted in dose reduction in 4% of treated patients and treatment discontinuation in 0.7%. Among patients with peripheral neuropathy after POLIVY, 58% reported resolution after a median of 4 months.

In Study GO29365, of 173 patients treated with POLIVY, 40% reported new or worsening peripheral neuropathy, with a median time to onset of 2.1 months. Peripheral neuropathy was Grade 1 in 26% of patients, Grade 2 in 12%, and Grade 3 in 2.3%. Peripheral neuropathy resulted in POLIVY dose reduction in 2.9% of treated patients, dose delay in 1.2%, and permanent discontinuation in 2.9%. Sixty-five percent of patients reported improvement or resolution of peripheral neuropathy after a median of 1 month, and 48% reported complete resolution.

The peripheral neuropathy is predominantly sensory; however, motor and sensorimotor peripheral neuropathy also occur. Monitor for symptoms of peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, or gait disturbance. Patients experiencing new or worsening peripheral neuropathy may require a delay, dose reduction, or discontinuation of POLIVY.

Infusion-Related Reactions

POLIVY can cause severe infusion reactions. Delayed infusion-related reactions as late as 24 hours after receiving POLIVY have occurred.

With premedication, 13% of patients (58/435) in POLARIX reported infusion-related reactions after the administration of POLIVY plus R-CHP. The reactions were Grade 1 in 4.4% of patients, Grade 2 in 8%, and Grade 3 in 1.1%.

With premedication, 7% of patients (12/173) in Study GO29365 reported infusion-related reactions after the administration of POLIVY. The reactions were Grade 1 in 4.6% of patients, Grade 2 in 1.7%, and Grade 3 in 0.6%.

Symptoms occurring in ≥1% of patients included chills, dyspnea, pyrexia, pruritus, rash, and chest discomfort. Administer an antihistamine and antipyretic prior to the administration of POLIVY, and monitor patients closely throughout the infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management.

Myelosuppression

Treatment with POLIVY can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia.

In POLARIX, 90% of patients treated with POLIVY plus R-CHP had primary prophylaxis with granulocyte colony-stimulating factor (G-CSF). Grade 3–4 hematologic adverse reactions included lymphopenia (44%), neutropenia (39%), febrile neutropenia (15%), anemia (14%), and thrombocytopenia (8%).

In Study GO29365, in patients treated with POLIVY plus BR (n = 45), 42% received primary prophylaxis with G-CSF. Grade 3 or higher hematologic adverse reactions included neutropenia (42%), thrombocytopenia (40%), anemia (24%), lymphopenia (13%), and febrile neutropenia (11%). Grade 4 hematologic adverse reactions included neutropenia (24%), thrombocytopenia (16%), lymphopenia (9%), and febrile neutropenia (4.4%). Cytopenias were the most common reason for treatment discontinuation (18% of all patients).

Monitor complete blood counts throughout treatment. Cytopenias may require a delay, dose reduction, or discontinuation of POLIVY. Administer prophylactic G-CSF for neutropenia in patients receiving POLIVY plus R-CHP. Consider prophylactic G-CSF administration in patients receiving POLIVY plus bendamustine and a rituximab product.

Serious and Opportunistic Infections

Fatal and/or serious infections, including opportunistic infections such as sepsis, pneumonia (including Pneumocystis jiroveci and other fungal pneumonia), herpesvirus infection, and cytomegalovirus infection have occurred in patients treated with POLIVY.

In POLARIX, Grade 3–4 infections occurred in 14% (61/435) of patients treated with POLIVY plus R-CHP, and infection-related deaths were reported in 1.1% of patients.

In Study GO29365, Grade 3 or higher infections occurred in 32% (55/173) of patients treated with POLIVY, and infection-related deaths were reported in 2.9% of patients within 90 days of last treatment.

Closely monitor patients during treatment for signs of infection. Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus. Administer prophylactic G-CSF for neutropenia as recommended.

Progressive Multifocal Leukoencephalopathy (PML)

PML has been reported after treatment with POLIVY plus bendamustine and obinutuzumab in Study GO29365 (0.6%, 1/173). Monitor for new or worsening neurological, cognitive, or behavioral changes. Hold POLIVY and any concomitant chemotherapy if PML is suspected, and permanently discontinue if the diagnosis is confirmed.

Tumor Lysis Syndrome

POLIVY may cause tumor lysis syndrome. Patients with high tumor burden and rapidly proliferative tumor may be at increased risk of tumor lysis syndrome. Monitor closely and take appropriate measures, including tumor lysis syndrome prophylaxis.

Hepatotoxicity

Serious cases of hepatotoxicity that were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, have occurred in patients treated with POLIVY.

In recipients of POLIVY plus R-CHP, Grade 3–4 elevation of ALT and AST developed in 1.4% and 0.7% of patients, respectively.

In Study GO29365, Grade 3 and Grade 4 transaminase elevations each developed in 1.9% of patients.

Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk of hepatotoxicity. Monitor liver enzymes and bilirubin level.

Embryo-Fetal Toxicity

Based on the mechanism of action and findings from animal studies, POLIVY can cause fetal harm when administered to a pregnant woman. The small molecule component of POLIVY, monomethyl auristatin E, administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures below those occurring clinically at the recommended dose.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with POLIVY and for 3 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with POLIVY and for 5 months after the last dose.

The Most Common Adverse Reactions

The most common adverse reactions (≥20%), excluding laboratory abnormalities, in patients with previously untreated DLBCL treated with POLIVY in combination with R-CHP are peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common Grade 3 to 4 laboratory abnormalities (≥10%) are lymphopenia, neutropenia, hyperuricemia, and anemia.

The most common adverse reactions (≥20%) in patients with relapsed or refractory DLBCL treated with POLIVY in combination with BR are neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.

Lactation

Advise women not to breastfeed during treatment with POLIVY and for 2 months after the last dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.
Please see the full Prescribing Information for additional Important Safety Information.

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